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Aline Bobato Lara Gongora



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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-67 - Metastatic RET-Rearranged Lung Adenocarcinomas Treated with Alectinib: Retrospective Analysis of a Single Institution (Now Available) (ID 745)

      10:15 - 18:15  |  Author(s): Aline Bobato Lara Gongora

      • Abstract
      • Slides

      Background

      RET-rearrangements are well-described drivers in lung adenocarcinomas (LADC), identified in nearly 1-2% of the tumors, for which there are no current specific targeted therapies approved. Although several tyrosine-kinase inhibitors (TKI) (e.g vandetanib, cabozantinib, lenvatinib, etc) demonstrate anti-RET activity, poor tolerability and overall response rates less than 50% has been limiting its widespread adoption. The structural homology between the kinase domains of ALK and RET, as well as the documented in vitroactivity, and well-known toxicity profile makes alectinib an attractive drug for evaluation in clinical trials and, possibly, for off-label use in the setting of progression upon pemetrexed-based chemotherapy.

      Method

      Retrospective assessment of the clinical and molecular characteristics, drug efficacy and tolerability of RET-rearranged LADC patients treated with alectinib in a single institution.

      Result

      Among the four patients identified, 100% were white, female and non-smokers, between 59-66 years old; 2/4 presented with high carcinoembryonic antigen levels and 1/4 with poorly differentiated LADC. All patients were TKI naïve and underwent evaluation with FoundationOne® next-generation sequencing platform, which showed KIF5B-RETfusion in 3/4 (75%) and CCDC6-RETin 1/4 (25%) of the cases. Among other alterations shared, 3/4 (75%) presented with CDKN2A/Bloss; in all cases, the tumors were microssatelite stable (MSS) and had low tumor mutational burden (1-9 muts/Mb). All patients were treated with 600 mg bid of alectinib. Among the four patients assessed, one was not available for radiological response evaluation and the drug was withheld within two months of treatment due to clinical deterioration. The best ORR was partial response in 2/4 (50%), with PFS ranging from 4-5 months. In one patient, after 5 months of therapy, an asymptomatic oligoprogression in soft-tissue was observed; the patient was treated with local radiation therapy and remains on alectinib for 12 months. No grade 3/4 adverse events, dose reductions or discontinuation due to toxicity were observed.

      Conclusion

      Although this is a small single center evaluation, alectinib demonstrated clinical activity in RET-rearranged LADC, apart from being a well-tolerated treatment. Nevertheless, the concurrent molecular alterations, its prognostic significance, the ideal dosing regimen and the precise magnitude of benefit are all questions to be addressed in clinical trials, in order to consider alectinib a treatment option for this small subset of patients.

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